- Email: [email protected]
Intraocular Tumors
Intraocular Tumors Evelyn X. Fu, MD, Brandy C. Hayden, BS, Arun D. Singh, MD* KEYWORDS Retinoblastoma Choroidal melanoma Choroidal hemangioma Choroidal metastasis Astrocytic hamartoma Choroidal osteoma
RETINOBLASTOMA Retinoblastoma is an important differential diagnosis in children presenting with leukocoria. The clinical presentation of retinoblastoma varies with the stage of the disease at the time of recognition. In its earliest clinical stage, retinoblastoma presents as a flat transparent to slightly white lesion in the sensory retina. As the tumor enlarges, it loses its transparency and becomes creamy yellow-white with foci of chalk-like calcification. As these tumors leave the confines of the retina with continued growth, they assume either an endophytic or exophytic pattern. Endophytic retinoblastomas grow from the retina inward toward the vitreous cavity. Seeding from these friable tumors in the vitreous and anterior chamber can simulate endophthalmitis and other inflammatory conditions. Exophytic retinoblastomas grow from the retina outward into the subretinal space and can cause exudative retinal detachment, sometimes displacing the retina anteriorly behind the lens. Advanced retinoblastoma can present with
neovascular glaucoma with corneal edema, spontaneous hyphema, vitreous hemorrhage, pseudohypopyon, and vitritis. Ultrasonography is very valuable in detecting retinoblastoma and differentiating it from other causes of leukocoria, particularly when funduscopic examination is limited in advanced cases. The internal reflectivity of these lesions varies according to the degree of calcification within the lesion. Noncalcified tumors show low-to-medium reflectivity, whereas calcified lesions exhibit high reflectivity (Fig. 1). With significant calcification, shadowing of the adjacent sclera and orbit occurs. B-scan typically displays a rounded or irregular intraocular mass. Mildly elevated diffuse lesions, however, have been reported.1,2 Depending on the clinical presentation, associated ultrasonographic findings may include retinal detachment and vitreal opacities (Fig. 2). Retinoblastoma has a predilection to invade the optic nerve and extend extraocularly. Optic nerve involvement and extraocular extension can be difficult to detect with ultrasound because of shadowing in cases with extensive calcification. CT and MR imaging should be used when optic nerve or extraocular invasion is suspected.
DIFFERENTIAL DIAGNOSIS OF RETINOBLASTOMA Numerous childhood ocular conditions can cause leukocoria and therefore simulate retinoblastoma. The conditions that most commonly present a diagnostic challenge include retinopathy of prematurity (ROP), persistent hyperplastic primary vitreous (PHPV), Coats’ disease, toxocariasis, and medulloepithelioma (Table 1).
Department of Ophthalmic Oncology, Cole Eye Institute (i-32), 9500 Euclid Avenue, Cleveland Clinic, Cleveland, OH 44195, USA * Corresponding author. E-mail address: [email protected] (A.D. Singh). Ultrasound Clin 3 (2008) 229–244 doi:10.1016/j.cult.2008.04.002 1556-858X/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved.
ultrasound.theclinics.com
Ultrasonography is a powerful noninvasive tool for the accurate diagnosis and effective management of intraocular tumors. Distinguishing ultrasonographic characteristics of intraocular tumors result from their different histopathologic compositions that can be evaluated with one-dimensional reflectivity analysis (A-scan) and two-dimensional acoustic section (B-scan). Information regarding location, shape, and acoustic characteristics is considered together to aid the diagnosis of intraocular tumors. Determination of size progression and extension is critical in selecting and monitoring management.
230
Fu et al
Fig.1. Retinoblastoma with calcification. Fundus photograph (A). Transverse B-scans demonstrate a large, domeshaped lesion with marked internal calcification. High gain showing the lesional boundaries (B, arrows). Low gain showing internal calcification causing shadowing of the orbit (C, arrow).
Retinopathy of Prematurity ROP is usually bilateral, with most patients having some degree of short axial length. In severe cases, the retina is dragged toward the fibrovascular lesion in the periphery, producing leukocoria. In
the most advanced cases, the retina is detached in a funnel-like configuration, resulting in a hyperreflective retrolental membrane on the B-scan. The peripheral retina frequently exhibits a loop or trough-like appearance as a result of traction by the retrolental membrane (Fig. 3).
Fig. 2. Retinoblastoma with associated retinal detachment. Fundus photograph (A). Longitudinal B-scan demonstrates a large, dome-shaped lesion with internal calcification (back arrow) and retinal detachment (white arrow) over the apex of the lesion and extending peripherally (B).
Intraocular Tumors
Table 1 Differential diagnosis of retinoblastoma Condition
Presentation
Laterality
Axial Length
USG Characteristics
Retinoblastoma
Few months to <2 years; possible family history Days to few months after birth; prematurity; oxygen supplementation Days to weeks after birth 4–10 years; most commonly males
Unilateral Bilateral Bilateral
Normal Short
Intraretinal/subretinal mass with calcification RD with retinal loops
Unilateral
Short
Unilateral
Normal
Toxocariasis
Contact with dogs
Unilateral
Normal
Medulloepithelioma
First decade of life
Unilateral
Normal
ROP
PHPV Coats’ disease
Vitreous band from lens to optic nerve Exudative RD Subretinal hyperreflective particles Peripheral mass, vitreoretinal band, traction RD Ciliary body mass with cyst
Abbreviations: PHPV, persistent hyperplastic primary vitreous; RD, retinal detachment; ROP, retinopathy of prematurity; USG, Ultrasonography.
Persistent Hyperplastic Primary Vitreous PHPV is a congenital condition that usually presents during the first few days or weeks of life. In contrast, retinoblastoma typically presents months after birth. In most cases, PHPV is a unilateral condition in a micro-ophthalmic eye. On B-scan, the lens is often thin, and the posterior capsule is irregular (Fig. 4). A retrolental membrane on the posterior surface of the lens with a vitreal band extending from this membrane to the optic disc is characteristic. The vitreal band
Fig. 3. Retinopathy of prematurity. Longitudinal B-scan demonstrates a highly reflective, closed funnel-shaped retinal detachment (arrows) inserting into the disc.
may be extremely thin, and its entire course may not be visualized. Some vitreal bands can be extremely thick and can simulate a tightly closed, funnel-shaped retinal detachment (see Fig. 4).
Coats’ Disease Coats’ disease is a unilateral retinal vascular disorder characterized by telangiectasia, intraretinal exudation, and exudative retinal detachment. Although Coats’ disease can present at any age, it usually is diagnosed in young males between 4 and 10 years of age.3 Retinoblastoma, however, has no sex predilection and typically is diagnosed before 2 years of age. In early stages of Coats’ disease, localized, shallow retinal detachments may occur (Fig. 5). Eyes with more advanced disease, however, present with total exudative detachments as a result of leakage from the aneurysmal blood vessels. Cholesterol crystals left in the subretinal space from the exudation are observed clinically as refractile particles. These particles are much less reflective than the calcium particles in retinoblastoma. Ultrasonography is valuable by demonstrating a tumor beneath the retinal detachment in retinoblastoma, whereas no distinct tumor can be shown in Coats’ disease.4
Toxocariasis Toxocariasis is caused by infestation of the eye with Toxocara canis. Ocular toxocariasis may
231
232
Fu et al
Fig. 4. Persistent hyperplastic primary vitreous. Fundus photograph (A). Longitudinal B-scan demonstrates taunt, thickened vitreous band adherent to the slightly elevated optic disc (B, arrow).
present as large retinal inflammatory masses with diffuse vitritis and simulate endophytic retinoblastoma. It also may resemble exophytic retinoblastoma by presenting as a solitary subretinal granuloma with little vitreous reaction. These chorioretinal masses most commonly are located in the peripheral fundus and produce vitreoretinal bands that can extend from the masses to the optic disc. Contraction of these vitreoretinal membranes can lead to tractional retinal detachments that are extremely rare in eyes with retinoblastoma. Ultrasonography that demonstrates vitreous traction bands or tractional retinal folds or detachments are characteristic of ocular toxocariasis (see the article by Ventura and colleagues, elsewhere in this issue).
Medulloepithelioma
decade of life.5 It most commonly arises from the ciliary body.6 Involvement of the iris and optic nerve, however, has been reported.7–10 Medulloepithelioma is an important differential diagnosis of leukocoria. It presents as an irregular white or gray translucent mass. The presence of cysts within the tumor is a characteristic feature. Large cysts may break off from the tumor and float freely in the anterior chamber or vitreous cavity. A scan shows mainly high internal reflectivity with medium spike height from cystic areas. On B-scan, these lesions are often dome-shaped, highly reflective with irregular internal structures. Cystic spaces can be demonstrated in some lesions (Fig. 6).
BENIGN UVEAL TUMORS Iris and Ciliary Body Nevus
Medulloepithelioma is a nonhereditary congenital tumor that typically manifests during the first
Iris and ciliar ciliary (spell) body nevus are evaluated best by ultrasound biomicroscopy, which should be used to determine tumor size, posterior
Fig. 5. Coats’ Disease. B-scan ultrasonograph showing funnel-shaped total retinal detachment (arrows). Note absence of an associated mass and that the retina is thickened.
Fig. 6. Medulloepithelioma. Ultrasound biomicroscopy showing a solid mass in the ciliary body with cystic cavities.
Intraocular Tumors extension, and internal consistency (see the article by Pavlin and colleagues, elsewhere in this issue).
Choroidal Nevus The Collaborative Ocular Melanoma Study (COMS) Group defined choroidal nevi as melanocytic lesions less than 5 mm in largest basal dimension and less than 1 mm in height.11 Ultrasonographic differentiation between choroidal nevi and small melanoma is difficult because of their small size. These lesions are often too flat to be detected by ultrasound. Suspicious nevi should be observed closely for changes in size. Nevi that are elevated enough for detection appear highly reflective and can be confused with other lesions with high reflectivity, such as choroidal hemangioma, metastatic carcinoma, and disciform lesions (Fig. 7).
elevated mildly and dome-shaped. They are typically highly reflective with regular internal structure and no internal vascularity (Fig. 8). Most melanocytomas remain stable,14–16 but subtle growth over several years is observed in approximately 10% of the cases.17,18 Malignant transformation into melanoma is reported in less than 2% of the cases.13–15,18–20
MALIGNANT UVEAL TUMORS Iris and Ciliary Body Melanoma Immersion techniques and high frequency ultrasound biomicroscopy are better suited than conventional contact ultrasonography for assessing iris and ciliary body melanomas because of their anterior location and smaller lesion size (See the article by Pavlin and colleagues, elsewhere in this issue).
Uveal Melanocytoma
Choroidal Melanoma
Melanocytomas are benign dark brown or black tumors that predominantly involve the optic disc and the surrounding choroid and retina. Isolated melanocytoma of the iris, ciliary body, and choroid have been reported.12–14 These lesions are
Choroidal melanomas exhibit various growth patterns. Small lesions typically appear as domeshaped, well-circumscribed, pigmented thickening of the choroids. As the lesions grow, the Bruch’s membrane may rupture to allow invasion
Fig.7. Choroidal nevus. Fundus photograph (A). Transverse B-scan demonstrates a dome-shaped choroidal lesion (B). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is medium-high reflective (C, arrows).
233
234
Fu et al
Fig. 8. Optic disc melanocytoma. Fundus photograph (A). Axial B-scan demonstrates a shallow, minimally elevated, dome-shaped lesion overlying the optic disc (B).
of the retina and extension into the vitreous cavity. If the Bruch’s membrane ruptures at the apex of the tumor, the lesion assumes a mushroom or collar button shape. When the Bruch’s membrane is ruptured at the rim of the tumor, it develops an irregular and inclined shape. Diffuse melanoma grows as an extensive thickening of the choroid and does not become elevated markedly. Regardless of their clinical presentation, all choroidal melanomas demonstrate characteristic ultrasonographic features (Box 1). A-scan Choroidal melanomas typically demonstrate lowto-medium internal reflectivity because of their homogeneous histologic architecture (Fig. 9). In larger lesions, sound attenuation is often observed with lower reflectivity at the base of the tumor. This is caused in part by the more homogeneous nature of the mass in this region. Moreover, lesions that contain hemorrhage, necrosis,
Box 1 Ultrasonographic features of uveal melanoma A-scan Low–medium reflectivity Sound attenuation Fast, spontaneous, low-amplitude flicker B-scan Collar button/dome shape Solid consistency Acoustic quiet zone Choroidal excavation Intrinsic vascular pulsations
and dilated vessels may show higher and more irregular internal reflectivity. Internal blood flow is another important acoustic property and can be appreciated by the presence of a fast, spontaneous, low-amplitude flickering within the internal tumor spikes. B-scan The pathognomonic appearance of choroidal melanoma is the collar button shape that results from a break in the Bruch’s membrane (Fig. 10). However, choroidal melanomas confined to the subretinal space, are dome-shaped, lobulated, and diffuse (see Fig. 9). Choroidal melanoma appears on B-scan as an echo-dense lesion. The reflectivity is caused by internal acoustic interfaces between the cellular mass and varying degree of vascularity. At the tumor base, where the mass is more homogeneously cellular, and in relatively avascular lesions, an echolucent area can be seen. This area is called the acoustic quiet zone or acoustic hollowing.21 As the neoplasm infiltrates the normal surrounding choroid, it causes a bowl-shaped indentation at the margin of the tumor base. This feature is called choroidal excavation. It is not specific for melanoma and has been demonstrated in metastatic carcinoma.22 Bowing of the sclera posterior to the tumor has been reported in younger individuals and may indicate scleral infiltration.23 Exudative retinal detachment, subretinal hemorrhage, and vitreous hemorrhage often occur secondary to choroidal melanoma. Dense subretinal and/or vitreal hemorrhages potentially can mask the underlying tumor. In these cases, serial examinations must be performed to rule out choroidal melanoma and other tumors. Extrascleral extension of choroidal melanoma appears as nodules near the base of the tumor.
Intraocular Tumors
Fig. 9. Choroidal melanoma. Fundus photograph (A). Longitudinal B-scan demonstrates a dome-shaped lesion with slightly sloping shoulders (B). Diagnostic A-scan directed perpendicular to the lesion shows the lesion is regularly structured and low reflective (C, arrows). Lobulated choroidal melanoma. Transverse B-scan demonstrates a large, lobulated lesion filling most of the vitreous space (D). Diffuse choroidal melanoma. Transverse B-scan demonstrates an irregularly shaped, diffuse choroidal lesion (E).
These nodules are often echolucent because of sound attenuation from the primary mass. Congested blood vessels, extraocular muscle insertion, and inflammation in the sub-Tenon space can be mistaken for extrascleral growth (Fig. 11). These misinterpretations, however, may be avoided by serial examinations and being aware of the location and normal appearance of the extraocular muscle.
Ultrasonographic diagnosis of a diffuse melanoma can be challenging. Internal reflectivity is often difficult to assess because of its shallow nature. On B-scan, these tumors may have an irregular surface. Because of increased incidences of extrascleral extension,24 alternate imaging techniques such as MR I and fine needle aspiration biopsy should be considered in suspicious The ultrasonographic differential cases.25
235
236
Fu et al
Fig. 10. Choroidal melanoma: collar button shape. Fundus photograph (A). Longitudinal B-scan demonstrates a collar button-shaped choroidal lesion with a defined segmentation corresponding to Bruch’s membrane (B, arrow). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is low reflective (arrows) with a single highly reflective spike corresponding to Bruch’s membrane (C, arrowhead).
Fig.11. Choroidal melanoma with extraocular extension. B-scan ultrasonography demonstrating a nodular extrascleral extension along the base of a relatively flat intraocular tumor (A, arrows). The extrascleral extension of the tumor should be differentiated from the extraocular muscles, which have flat configuration and appear to separate from the sclera when traced posteriorly corresponding to the normal anatomic location of the muscle (B, arrows). (From Singh AD, Rundle PA, Berry–Brincat A, et al. Extrascleral extension of choroidal malignant melanoma following transpupillary thermotherapy. Eye 2004;18:92; with permission.)
Intraocular Tumors diagnosis of diffuse melanoma includes metastatic carcinoma, diffuse choroidal hemangioma, uveal lymphoid hyperplasia, diffuse choroidal nevus, and Vog-Koyanagi-Harada syndrome.
Fig. 12. Placement of iodine-125 radiation plaque. Transverse B-scan demonstrates a dome-shaped intraocular lesion with a concave radiation plaque behind the lesion and adjacent to the sclera. The highly reflective linear points within the plaque correspond to the I-125 seeds (arrow heads). Note that the margins of the tumor (arrows) are well within the margins of the plaque (lines).
Tumor biometry Ultrasonography plays a critical role in managing and monitoring uveal melanoma by providing accurate measurements of tumor dimensions. Apical height of uveal melanomas can be determined using the A- or B-scan. In small tumors (less than 1.5 mm), A-scan measurements can be challenging, and B-scan is recommended. The measurements obtained with these two methods should be within 0.2 to 0.3 mm for medium tumors and 0.5 mm for large tumors. When the retina is attached to the apex of the lesion, the tumor surface spike on the A-scan may appear thick, because it includes both the retina and tumor surface. In these cases, measurements should be obtained from the retinal portion of the surface spike. When the retina is detached, measurements should be taken from the tumor surface and not the retinal detachment. Basal diameter of
Fig. 13. Response to radiation plaque treatment. Fundus photograph before (A) and 1 year after treatment (B). Longitudinal B-scan of a collar button-shaped choroidal melanoma associated retinal detachment (C). Note marked decrease in height and resolution of the associated retinal detachment (D).
237
238
Fu et al
Table 2 Ultrasonographic features of lesions that simulate choroidal melanoma Lesion
Shape
Reflectivity
Attenuation
Vascularity
Specific Features
Melanoma
Collar button/dome/lobulated
Low-medium
High
High
Choroidal nevus
Flat/Dome
Low-medium
High
No
Choroidal hemangioma
Dome
High
No
No
Metastatic carcinoma ARMD/AREMD
Placoid/irregular/multiple Dome/irregular
Medium-high High
Low No
No No
Leiomyoma
Dome
Low-medium
No
No
Posterior scleritis
Dome
Medium-high
No
No
Regular internal structure Acoustic hollowness Choroidal excavation Height less than 2 mm Regular internal structure Multiple lesions Irregular internal structure Regular internal structure T sign
Abbreviation: ARMD/AREMD, age-related macular and extramacular degeneration.
Intraocular Tumors a uveal melanoma is determined with the transverse and longitudinal approaches of the B-scan. The transverse approach measures the circumferential diameter, while the longitudinal approach evaluates the radial diameter. Intraoperative confirmation of plaque placement Ultrasonagraphy is used commonly to assess proper placement of radioactive material in radiation therapy and evaluate the effectiveness of various treatments. In brachytherapy, localization of a plaque can be performed in the operating room under sterile conditions or postoperatively. It is particularly helpful in posterior tumors, where transillumination cannot indicate the tumor margins adequately. The iodine-125 plaque produces an echolucent pattern with marked shadowing of the orbital tissues (Fig. 12). Response to radiation therapy After radiation treatment, uveal melanoma becomes more irregular and reflective as necrosis
occurs. The tumor loses its internal vascularity and decreases in size, indicating effective treatment (Fig. 13). Some lesions initially enlarge as a result of edema, but most eventually reduce in size. Continued enlargement may signify true tumor growth. Additionally, long-term follow-up is recommended even in lesions with significant initial regression, as tumor growth has been reported in these cases.26,27
Differential Diagnosis of Choroidal Melanoma Several pigmented and nonpigmented lesions can resemble choroidal melanoma. Ultrasonography can be valuable to diagnose and differentiate the more common simulating lesions (Table 2). Circumscribed choroidal hemangioma Uveal hemangioma most frequently affects the choroid and presents as a circumscribed or diffuse orange-red, mildly elevated lesion. Circumscribed tumors are sporadic, usually located in the posterior pole, and dome-shaped with a thickness less
Fig. 14. Circumscribed choroidal hemangioma. Fundus photograph (A). Transverse B-scan demonstrating irregularly shaped choroidal lesion (B). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is highly reflective (C, arrows).
239
240
Fu et al
Fig. 15. Choroidal metastasis. Fundus photograph (A). Transverse B-scan demonstrating dome-shaped choroidal lesion (B). Diagnostic A-scan directed perpendicular to the lesion shows the lesion is slightly irregularly structured and is mainly medium-high reflective (C).
Fig. 16. Leiomyoma. High-frequency ultrasound scan demonstrating ciliary body leiomyoma resembling a melanoma. (From Rundle P, Mudhar HS, Parsons MA, et al. Uveal myogenic, fibrous, and histiocytic tumors. In: Singh AD, Damato BE, Pe’er J, et al, editors. Clinical Ophthalmic Oncology. Philadelphia: Saunders-Elsevier; 2007. p. 312; with permission.)
Fig. 17. Disciform lesion. Longitudinal B-scan demonstrating an irregularly shaped and structured lesion in the macula.
Intraocular Tumors
Fig. 18. Astrocystic hamartoma. Fundus photograph (A). Longitudinal B-scan demonstrating an oval mass with sharp borders and orbital shadowing (B). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is structured slightly irregularly and is highly reflective (C, arrows).
than 6 mm.28 Diffuse choroidal hemangiomas are a part of neuro-oculo-cutaneous hemangiomatosis (Sturge-Weber syndrome). These tumors often are less elevated than the circumscribed, domeshaped lesions and can be mistaken for nonspecific retinochoroidal thickening. As a result, the retinochoroid layer thickness must be compared carefully between the two eyes in cases with Sturge-Weber syndrome. On A-scan, choroidal hemangiomas exhibit high internal reflectivity with negligible attenuation. They are hyperechoic on B-scan with regular internal structure and little internal blood flow (Fig. 14). Serous retinal detachment at the tumor margins and calcification on the tumor surface may be present.28
degree of internal irregularity that results from the varied histologic architecture (Fig. 15). Internal vascularity is minimal or absent. On B-scan, these lesions have irregular surfaces and often central excavations. The serous retinal detachment is often much more extensive with metastatic carcinomas than with a comparable-sized choroidal melanoma. Vitreous and subretinal hemorrhages rarely are associated with metastatic carcinoma. Some choroidal metastases present with atypical features such as low internal reflectivity and internal vascularity. The most common metastasis to produce these atypical findings is small cell carcinoma of the lung. Additionally, bullous choroidal detachments have been reported.29
Choroidal metastasis Choroidal metastasis preferentially presents in the posterior pole as focal or multifocal lesions. They may be flat or dome-shaped, pigmented or nonpigmented, and unilateral or bilateral. They frequently are associated with serous retinal detachments. The internal reflectivity of metastatic carcinoma is typically medium to high with some
Leiomyoma Leiomyoma is a nonpigmented benign tumor that almost exclusively occurs in young women. Clinically, they can be differentiated from amelanotic choroidal melanoma by transillumination. Leiomyoma readily transilluminates, while choroidal melanoma does not. On B-scan, these lesions are smooth and dome-shaped. A scan shows
241
242
Fu et al
Box 2 Conditions associated with intraocular calcification Retinal and RPE lesions Retinoblastoma Astrocytic hamartoma Chronic retinal detachment RPE metaplasia Cysticercosis Choroidal lesions Choroidal osteoma Sclerochoroidal calcification Choroidal granuloma Others Optic nerve head drusen Scleral calcification (Cogan’s plaque) Phthisis bulbi
low-to-medium internal reflectivity with regular internal structure (Fig. 16).
Age-related macular and extramacular degeneration Exudative age-related macular and extramacular degeneration (ARMD/AREMD) with subretinal or sub-retinal pigment epithelium exudate or hemorrhage can resemble choroidal melanoma closely. Ultrasonographically, exudative ARMD/AREMD appears as a mass lesion with moderately high internal reflectivity. When the subretinal blood becomes organized, however, these lesions can display low internal reflectivity and choroidal
excavation, similar to that seen with a choroidal melanoma. Scarring, fibrosis, and calcification can occur in chronic stages of exudative ARMD/AREMD, leading to the formation of disciform lesions. Nonhemorrhagic disciform lesions appear as two or three highly reflective spikes on A-scan. On B-scan, they are mildly to moderately elevated, dome-shaped, and heterogeneous (see the article by Sharma and colleagues, elsewhere in this issue). Hemorrhagic disciform lesions can be localized or diffuse. They usually exhibit a bumpy, lobulated surface with indistinct margins. On ultrasonography, they display irregular internal structure with areas of high and low internal reflectivity as a result of fibrovascular proliferation, exudation, and clotted or unclotted hemorrhage (Fig. 17). Calcification and vitreous hemorrhage can be associated with these lesions. Unlike choroidal melanoma, internal vascularity is not present in these lesions. Serial examination of hemorrhagic disciform lesions can help distinguish them from choroidal melanomas. Hemorrhagic disciform lesions tend to decrease in size, whereas choroidal melanomas remain stable or increase in size. Very rarely, spontaneous regression of choroidal melanoma can occur.30 Posterior scleritis Nodular posterior scleritis appears as an elevated mass that can resemble an amelanotic choroidal melanoma closely. Ultrasonographic features of these lesions are described in the article by Ventura and colleagues, elsewhere in this issue.
INTRAOCULAR CALCIFICATION Intraocular calcification can result from several tumors and degenerative processes (Box 2).
Fig. 19. Choroidal osteoma. Fundus photograph (A). Vertical axial B-scan demonstrating a minimally elevated, highly reflective lesion causing orbital shadowing (B).
Intraocular Tumors
Fig. 20. Sclerochoroidal calcification. Fundus photograph (A). Transverse B-scan demonstrating an irregularly shaped, highly reflective fundus lesion with orbital shadowing (B).
Astrocytic Hamartoma
Others
Astrocytic hamartoma of the retina and optic disc is a benign tumor that typically occurs in patients who have tuberous sclerosis and neurofibromatosis. Small, noncalcified tumors can be extremely subtle and appear as ill-defined translucent thickening of the nerve fiber layer. Larger lesions become more opaque and appear as a sessile white lesion at the level of the nerve fiber layer. Some lesions contain characteristic dense yellow, refractile calcification that has been likened to mulberry or tapioca. Ultrasonography is of little diagnostic value in small, flat, noncalcified lesions. Larger calcified lesions, however, appear as welldemarcated oval masses with a high reflectivity, sharp anterior borders, and orbital shadowing on B-scan. A scan shows high internal reflectivity and attenuation of orbital echoes posterior to the tumor (Fig. 18).
Cogan’s plaques are focal areas of scleral calcification located anterior to the insertion of the horizontal rectii muscles. Chronic ocular inflammation or trauma can induce osseous metaplasia of the RPE with or without phthisis bulbi, which can be detected as intraocular calcification by ultrasonography.
Choroidal Osteoma Choroidal osteomas are composed of cancellous bone and present as yellow-white, minimally elevated, well-defined lesions in the juxtapapillary or peripapillary region. These lesions produce extremely high internal reflectivity on A-scan. They are very echo-dense on B-scan with significant orbital shadowing (Fig. 19).
Sclerochoroidal Calcification Sclerochoroidal calcification simulates choroidal osteoma ultrasonographically with high reflectivity and marked orbital shadowing. Distinction between these two entities is based on clinical features (Fig. 20).
REFERENCES 1. Shields CL, Shields JA, Shah P. Retinoblastoma in older children. Ophthalmology 1991;98:395–9. 2. All-Ericsson C, Economou MA, Landau I, et al. Uveitis masquerade syndromes: diffuse retinoblastoma in an older child. Acta Ophthalmol Scand 2007;85:569–70. 3. Ridley ME, Shields JA, Brown GC, et al. Coats’ disease. Evaluation of management. Ophthalmology 1982;89:1381–7. 4. Jaffe MS, Shields JA, Canny CL, et al. Retinoblastoma simulating Coats’ disease: a clinicopathologic report. Ann Ophthalmol 1977;9:863–8. 5. Shields JA, Eagle RC Jr, Shields CL, et al. Congenital neoplasms of the nonpigmented ciliary epithelium (medulloepithelioma). Ophthalmology 1996; 103:1998–2006. 6. Broughton WL, Zimmerman LE. A clinicopathologic study of 56 cases of intraocular medulloepitheliomas. Am J Ophthalmol 1978;85:407–18. 7. Morris AT, Garner A. Medulloepithelioma involving the iris. Br J Ophthalmol 1975;59:276–8. 8. Orellana J, Moura RA, Font RL, et al. Medulloepithelioma diagnosed by ultrasound and vitreous aspirate. Electron microscopic observations. Ophthalmology 1983;90:1531–9. 9. Green WR, Iliff WJ, Trotter RR. Malignant teratoid medulloepithelioma of the optic nerve. Arch Ophthalmol 1974;91:451–4.
243
244
Fu et al 10. Biswas J, Bhushan B, Jayakumar N, et al. Teratoid malignant medulloepithelioma of the optic nerve: report of a case and review of the literature. Orbit 1999;18:191–6. 11. Factors predictive of growth and treatment of small choroidal melanoma: COMS Report No. 5. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol 1997;115:1537–44. 12. Brownstein S, Dorey MW, Mathew B, et al. Melanocytoma of the choroid: atypical presentation and review of the literature. Can J Ophthalmol 2002;37(4):247–52. 13. Demirci H, Mashayekhi A, Shields CL, et al. Iris melanocytoma: clinical features and natural course in 47 cases. Am J Ophthalmol 2005;139:468–75. 14. LoRusso FJ, Boniuk M, Font RL. Melanocytoma (magnocellular nevus) of the ciliary body: report of 10 cases and review of the literature. Ophthalmology 2000;107:795–800. 15. Shields JA, Demirci H, Mashayekhi A, et al. Melanocytoma of optic disc in 115 cases: the 2004 Samuel Johnson Memorial Lecture, part 1. Ophthalmology 2004;111:1739–46. 16. Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytoma: nomenclature, pathogenesis, natural history, and treatment. Surv Ophthalmol 1985;29: 319–27. 17. Mansour AM, Zimmerman L, La Piana FG, et al. Clinicopathological findings in a growing optic nerve melanocytoma. Br J Ophthalmol 1989;73:410–5. 18. Roth AM. Malignant change in melanocytomas of the uveal tract. Surv Ophthalmol 1978;22:404–12. 19. Apple DJ, Craythorn JM, Reidy JJ, et al. Malignant transformation of an optic nerve melanocytoma. Can J Ophthalmol 1984;19:320–5. 20. Meyer D, Ge J, Blinder KJ, et al. Malignant transformation of an optic disk melanocytoma. Am J Ophthalmol 1999;127:710–4.
21. Goldberg MF, Hodes BL. Ultrasonographic diagnosis of choroidal malignant melanoma. Surv Ophthalmol 1977;22:29–40. 22. Fuller DG, Snyder WB, Hutton WL, et al. Ultrasonographic features of choroidal malignant melanomas. Arch Ophthalmol 1979;97:1465–72. 23. Cham MC, Pavlin CJ. Ultrasound detection of posterior scleral bowing in young patients with choroidal melanoma. Can J Ophthalmol 2000;35: 263–6. 24. Braun UC, Rummelt VC, Naumann GO. Diffuse maligne Melanome der Uvea. Eine klinisch-histopathologische Studie uber 39 Patienten. Klin Monatsbl Augenheilkd 1998;213:331–40. 25. Biswas J, Raghavendra R, Ratra V, et al. Diffuse malignant melanoma of the choroid-simulating metastatic tumour in the choroid. Indian J Ophthalmol 2000;48:137–40. 26. Gragoudas ES, Lane AM, Munzenrider J, et al. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans Am Ophthalmol Soc 2002;100:43–8. 27. Novak-Andrejcic K, Jancar B, Hawlina M. Echographic follow-up of malignant melanoma of the choroid after brachytherapy with 106Ru. Klin Monatsbl Augenheilkd 2003;220:853–60. 28. Witschel H, Font RL. Hemangioma of the choroid. A clinicopathologic study of 71 cases and a review of the literature. Surv Ophthalmol 1976;20:415–31. 29. Kreiger AE, Meyer D, Smith TR, et al. Metastatic carcinoma to the choroid with choroidal detachment. A case presenting as uveal effusion. Arch Ophthalmol 1969;82:209–13. 30. Shields CL, Shields JA, Santos MC, et al. Incomplete spontaneous regression of choroidal melanoma associated with inflammation. Arch Ophthalmol 1999; 117:1245–7.
RETINOBLASTOMA Retinoblastoma is an important differential diagnosis in children presenting with leukocoria. The clinical presentation of retinoblastoma varies with the stage of the disease at the time of recognition. In its earliest clinical stage, retinoblastoma presents as a flat transparent to slightly white lesion in the sensory retina. As the tumor enlarges, it loses its transparency and becomes creamy yellow-white with foci of chalk-like calcification. As these tumors leave the confines of the retina with continued growth, they assume either an endophytic or exophytic pattern. Endophytic retinoblastomas grow from the retina inward toward the vitreous cavity. Seeding from these friable tumors in the vitreous and anterior chamber can simulate endophthalmitis and other inflammatory conditions. Exophytic retinoblastomas grow from the retina outward into the subretinal space and can cause exudative retinal detachment, sometimes displacing the retina anteriorly behind the lens. Advanced retinoblastoma can present with
neovascular glaucoma with corneal edema, spontaneous hyphema, vitreous hemorrhage, pseudohypopyon, and vitritis. Ultrasonography is very valuable in detecting retinoblastoma and differentiating it from other causes of leukocoria, particularly when funduscopic examination is limited in advanced cases. The internal reflectivity of these lesions varies according to the degree of calcification within the lesion. Noncalcified tumors show low-to-medium reflectivity, whereas calcified lesions exhibit high reflectivity (Fig. 1). With significant calcification, shadowing of the adjacent sclera and orbit occurs. B-scan typically displays a rounded or irregular intraocular mass. Mildly elevated diffuse lesions, however, have been reported.1,2 Depending on the clinical presentation, associated ultrasonographic findings may include retinal detachment and vitreal opacities (Fig. 2). Retinoblastoma has a predilection to invade the optic nerve and extend extraocularly. Optic nerve involvement and extraocular extension can be difficult to detect with ultrasound because of shadowing in cases with extensive calcification. CT and MR imaging should be used when optic nerve or extraocular invasion is suspected.
DIFFERENTIAL DIAGNOSIS OF RETINOBLASTOMA Numerous childhood ocular conditions can cause leukocoria and therefore simulate retinoblastoma. The conditions that most commonly present a diagnostic challenge include retinopathy of prematurity (ROP), persistent hyperplastic primary vitreous (PHPV), Coats’ disease, toxocariasis, and medulloepithelioma (Table 1).
Department of Ophthalmic Oncology, Cole Eye Institute (i-32), 9500 Euclid Avenue, Cleveland Clinic, Cleveland, OH 44195, USA * Corresponding author. E-mail address: [email protected] (A.D. Singh). Ultrasound Clin 3 (2008) 229–244 doi:10.1016/j.cult.2008.04.002 1556-858X/08/$ – see front matter ª 2008 Elsevier Inc. All rights reserved.
ultrasound.theclinics.com
Ultrasonography is a powerful noninvasive tool for the accurate diagnosis and effective management of intraocular tumors. Distinguishing ultrasonographic characteristics of intraocular tumors result from their different histopathologic compositions that can be evaluated with one-dimensional reflectivity analysis (A-scan) and two-dimensional acoustic section (B-scan). Information regarding location, shape, and acoustic characteristics is considered together to aid the diagnosis of intraocular tumors. Determination of size progression and extension is critical in selecting and monitoring management.
230
Fu et al
Fig.1. Retinoblastoma with calcification. Fundus photograph (A). Transverse B-scans demonstrate a large, domeshaped lesion with marked internal calcification. High gain showing the lesional boundaries (B, arrows). Low gain showing internal calcification causing shadowing of the orbit (C, arrow).
Retinopathy of Prematurity ROP is usually bilateral, with most patients having some degree of short axial length. In severe cases, the retina is dragged toward the fibrovascular lesion in the periphery, producing leukocoria. In
the most advanced cases, the retina is detached in a funnel-like configuration, resulting in a hyperreflective retrolental membrane on the B-scan. The peripheral retina frequently exhibits a loop or trough-like appearance as a result of traction by the retrolental membrane (Fig. 3).
Fig. 2. Retinoblastoma with associated retinal detachment. Fundus photograph (A). Longitudinal B-scan demonstrates a large, dome-shaped lesion with internal calcification (back arrow) and retinal detachment (white arrow) over the apex of the lesion and extending peripherally (B).
Intraocular Tumors
Table 1 Differential diagnosis of retinoblastoma Condition
Presentation
Laterality
Axial Length
USG Characteristics
Retinoblastoma
Few months to <2 years; possible family history Days to few months after birth; prematurity; oxygen supplementation Days to weeks after birth 4–10 years; most commonly males
Unilateral Bilateral Bilateral
Normal Short
Intraretinal/subretinal mass with calcification RD with retinal loops
Unilateral
Short
Unilateral
Normal
Toxocariasis
Contact with dogs
Unilateral
Normal
Medulloepithelioma
First decade of life
Unilateral
Normal
ROP
PHPV Coats’ disease
Vitreous band from lens to optic nerve Exudative RD Subretinal hyperreflective particles Peripheral mass, vitreoretinal band, traction RD Ciliary body mass with cyst
Abbreviations: PHPV, persistent hyperplastic primary vitreous; RD, retinal detachment; ROP, retinopathy of prematurity; USG, Ultrasonography.
Persistent Hyperplastic Primary Vitreous PHPV is a congenital condition that usually presents during the first few days or weeks of life. In contrast, retinoblastoma typically presents months after birth. In most cases, PHPV is a unilateral condition in a micro-ophthalmic eye. On B-scan, the lens is often thin, and the posterior capsule is irregular (Fig. 4). A retrolental membrane on the posterior surface of the lens with a vitreal band extending from this membrane to the optic disc is characteristic. The vitreal band
Fig. 3. Retinopathy of prematurity. Longitudinal B-scan demonstrates a highly reflective, closed funnel-shaped retinal detachment (arrows) inserting into the disc.
may be extremely thin, and its entire course may not be visualized. Some vitreal bands can be extremely thick and can simulate a tightly closed, funnel-shaped retinal detachment (see Fig. 4).
Coats’ Disease Coats’ disease is a unilateral retinal vascular disorder characterized by telangiectasia, intraretinal exudation, and exudative retinal detachment. Although Coats’ disease can present at any age, it usually is diagnosed in young males between 4 and 10 years of age.3 Retinoblastoma, however, has no sex predilection and typically is diagnosed before 2 years of age. In early stages of Coats’ disease, localized, shallow retinal detachments may occur (Fig. 5). Eyes with more advanced disease, however, present with total exudative detachments as a result of leakage from the aneurysmal blood vessels. Cholesterol crystals left in the subretinal space from the exudation are observed clinically as refractile particles. These particles are much less reflective than the calcium particles in retinoblastoma. Ultrasonography is valuable by demonstrating a tumor beneath the retinal detachment in retinoblastoma, whereas no distinct tumor can be shown in Coats’ disease.4
Toxocariasis Toxocariasis is caused by infestation of the eye with Toxocara canis. Ocular toxocariasis may
231
232
Fu et al
Fig. 4. Persistent hyperplastic primary vitreous. Fundus photograph (A). Longitudinal B-scan demonstrates taunt, thickened vitreous band adherent to the slightly elevated optic disc (B, arrow).
present as large retinal inflammatory masses with diffuse vitritis and simulate endophytic retinoblastoma. It also may resemble exophytic retinoblastoma by presenting as a solitary subretinal granuloma with little vitreous reaction. These chorioretinal masses most commonly are located in the peripheral fundus and produce vitreoretinal bands that can extend from the masses to the optic disc. Contraction of these vitreoretinal membranes can lead to tractional retinal detachments that are extremely rare in eyes with retinoblastoma. Ultrasonography that demonstrates vitreous traction bands or tractional retinal folds or detachments are characteristic of ocular toxocariasis (see the article by Ventura and colleagues, elsewhere in this issue).
Medulloepithelioma
decade of life.5 It most commonly arises from the ciliary body.6 Involvement of the iris and optic nerve, however, has been reported.7–10 Medulloepithelioma is an important differential diagnosis of leukocoria. It presents as an irregular white or gray translucent mass. The presence of cysts within the tumor is a characteristic feature. Large cysts may break off from the tumor and float freely in the anterior chamber or vitreous cavity. A scan shows mainly high internal reflectivity with medium spike height from cystic areas. On B-scan, these lesions are often dome-shaped, highly reflective with irregular internal structures. Cystic spaces can be demonstrated in some lesions (Fig. 6).
BENIGN UVEAL TUMORS Iris and Ciliary Body Nevus
Medulloepithelioma is a nonhereditary congenital tumor that typically manifests during the first
Iris and ciliar ciliary (spell) body nevus are evaluated best by ultrasound biomicroscopy, which should be used to determine tumor size, posterior
Fig. 5. Coats’ Disease. B-scan ultrasonograph showing funnel-shaped total retinal detachment (arrows). Note absence of an associated mass and that the retina is thickened.
Fig. 6. Medulloepithelioma. Ultrasound biomicroscopy showing a solid mass in the ciliary body with cystic cavities.
Intraocular Tumors extension, and internal consistency (see the article by Pavlin and colleagues, elsewhere in this issue).
Choroidal Nevus The Collaborative Ocular Melanoma Study (COMS) Group defined choroidal nevi as melanocytic lesions less than 5 mm in largest basal dimension and less than 1 mm in height.11 Ultrasonographic differentiation between choroidal nevi and small melanoma is difficult because of their small size. These lesions are often too flat to be detected by ultrasound. Suspicious nevi should be observed closely for changes in size. Nevi that are elevated enough for detection appear highly reflective and can be confused with other lesions with high reflectivity, such as choroidal hemangioma, metastatic carcinoma, and disciform lesions (Fig. 7).
elevated mildly and dome-shaped. They are typically highly reflective with regular internal structure and no internal vascularity (Fig. 8). Most melanocytomas remain stable,14–16 but subtle growth over several years is observed in approximately 10% of the cases.17,18 Malignant transformation into melanoma is reported in less than 2% of the cases.13–15,18–20
MALIGNANT UVEAL TUMORS Iris and Ciliary Body Melanoma Immersion techniques and high frequency ultrasound biomicroscopy are better suited than conventional contact ultrasonography for assessing iris and ciliary body melanomas because of their anterior location and smaller lesion size (See the article by Pavlin and colleagues, elsewhere in this issue).
Uveal Melanocytoma
Choroidal Melanoma
Melanocytomas are benign dark brown or black tumors that predominantly involve the optic disc and the surrounding choroid and retina. Isolated melanocytoma of the iris, ciliary body, and choroid have been reported.12–14 These lesions are
Choroidal melanomas exhibit various growth patterns. Small lesions typically appear as domeshaped, well-circumscribed, pigmented thickening of the choroids. As the lesions grow, the Bruch’s membrane may rupture to allow invasion
Fig.7. Choroidal nevus. Fundus photograph (A). Transverse B-scan demonstrates a dome-shaped choroidal lesion (B). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is medium-high reflective (C, arrows).
233
234
Fu et al
Fig. 8. Optic disc melanocytoma. Fundus photograph (A). Axial B-scan demonstrates a shallow, minimally elevated, dome-shaped lesion overlying the optic disc (B).
of the retina and extension into the vitreous cavity. If the Bruch’s membrane ruptures at the apex of the tumor, the lesion assumes a mushroom or collar button shape. When the Bruch’s membrane is ruptured at the rim of the tumor, it develops an irregular and inclined shape. Diffuse melanoma grows as an extensive thickening of the choroid and does not become elevated markedly. Regardless of their clinical presentation, all choroidal melanomas demonstrate characteristic ultrasonographic features (Box 1). A-scan Choroidal melanomas typically demonstrate lowto-medium internal reflectivity because of their homogeneous histologic architecture (Fig. 9). In larger lesions, sound attenuation is often observed with lower reflectivity at the base of the tumor. This is caused in part by the more homogeneous nature of the mass in this region. Moreover, lesions that contain hemorrhage, necrosis,
Box 1 Ultrasonographic features of uveal melanoma A-scan Low–medium reflectivity Sound attenuation Fast, spontaneous, low-amplitude flicker B-scan Collar button/dome shape Solid consistency Acoustic quiet zone Choroidal excavation Intrinsic vascular pulsations
and dilated vessels may show higher and more irregular internal reflectivity. Internal blood flow is another important acoustic property and can be appreciated by the presence of a fast, spontaneous, low-amplitude flickering within the internal tumor spikes. B-scan The pathognomonic appearance of choroidal melanoma is the collar button shape that results from a break in the Bruch’s membrane (Fig. 10). However, choroidal melanomas confined to the subretinal space, are dome-shaped, lobulated, and diffuse (see Fig. 9). Choroidal melanoma appears on B-scan as an echo-dense lesion. The reflectivity is caused by internal acoustic interfaces between the cellular mass and varying degree of vascularity. At the tumor base, where the mass is more homogeneously cellular, and in relatively avascular lesions, an echolucent area can be seen. This area is called the acoustic quiet zone or acoustic hollowing.21 As the neoplasm infiltrates the normal surrounding choroid, it causes a bowl-shaped indentation at the margin of the tumor base. This feature is called choroidal excavation. It is not specific for melanoma and has been demonstrated in metastatic carcinoma.22 Bowing of the sclera posterior to the tumor has been reported in younger individuals and may indicate scleral infiltration.23 Exudative retinal detachment, subretinal hemorrhage, and vitreous hemorrhage often occur secondary to choroidal melanoma. Dense subretinal and/or vitreal hemorrhages potentially can mask the underlying tumor. In these cases, serial examinations must be performed to rule out choroidal melanoma and other tumors. Extrascleral extension of choroidal melanoma appears as nodules near the base of the tumor.
Intraocular Tumors
Fig. 9. Choroidal melanoma. Fundus photograph (A). Longitudinal B-scan demonstrates a dome-shaped lesion with slightly sloping shoulders (B). Diagnostic A-scan directed perpendicular to the lesion shows the lesion is regularly structured and low reflective (C, arrows). Lobulated choroidal melanoma. Transverse B-scan demonstrates a large, lobulated lesion filling most of the vitreous space (D). Diffuse choroidal melanoma. Transverse B-scan demonstrates an irregularly shaped, diffuse choroidal lesion (E).
These nodules are often echolucent because of sound attenuation from the primary mass. Congested blood vessels, extraocular muscle insertion, and inflammation in the sub-Tenon space can be mistaken for extrascleral growth (Fig. 11). These misinterpretations, however, may be avoided by serial examinations and being aware of the location and normal appearance of the extraocular muscle.
Ultrasonographic diagnosis of a diffuse melanoma can be challenging. Internal reflectivity is often difficult to assess because of its shallow nature. On B-scan, these tumors may have an irregular surface. Because of increased incidences of extrascleral extension,24 alternate imaging techniques such as MR I and fine needle aspiration biopsy should be considered in suspicious The ultrasonographic differential cases.25
235
236
Fu et al
Fig. 10. Choroidal melanoma: collar button shape. Fundus photograph (A). Longitudinal B-scan demonstrates a collar button-shaped choroidal lesion with a defined segmentation corresponding to Bruch’s membrane (B, arrow). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is low reflective (arrows) with a single highly reflective spike corresponding to Bruch’s membrane (C, arrowhead).
Fig.11. Choroidal melanoma with extraocular extension. B-scan ultrasonography demonstrating a nodular extrascleral extension along the base of a relatively flat intraocular tumor (A, arrows). The extrascleral extension of the tumor should be differentiated from the extraocular muscles, which have flat configuration and appear to separate from the sclera when traced posteriorly corresponding to the normal anatomic location of the muscle (B, arrows). (From Singh AD, Rundle PA, Berry–Brincat A, et al. Extrascleral extension of choroidal malignant melanoma following transpupillary thermotherapy. Eye 2004;18:92; with permission.)
Intraocular Tumors diagnosis of diffuse melanoma includes metastatic carcinoma, diffuse choroidal hemangioma, uveal lymphoid hyperplasia, diffuse choroidal nevus, and Vog-Koyanagi-Harada syndrome.
Fig. 12. Placement of iodine-125 radiation plaque. Transverse B-scan demonstrates a dome-shaped intraocular lesion with a concave radiation plaque behind the lesion and adjacent to the sclera. The highly reflective linear points within the plaque correspond to the I-125 seeds (arrow heads). Note that the margins of the tumor (arrows) are well within the margins of the plaque (lines).
Tumor biometry Ultrasonography plays a critical role in managing and monitoring uveal melanoma by providing accurate measurements of tumor dimensions. Apical height of uveal melanomas can be determined using the A- or B-scan. In small tumors (less than 1.5 mm), A-scan measurements can be challenging, and B-scan is recommended. The measurements obtained with these two methods should be within 0.2 to 0.3 mm for medium tumors and 0.5 mm for large tumors. When the retina is attached to the apex of the lesion, the tumor surface spike on the A-scan may appear thick, because it includes both the retina and tumor surface. In these cases, measurements should be obtained from the retinal portion of the surface spike. When the retina is detached, measurements should be taken from the tumor surface and not the retinal detachment. Basal diameter of
Fig. 13. Response to radiation plaque treatment. Fundus photograph before (A) and 1 year after treatment (B). Longitudinal B-scan of a collar button-shaped choroidal melanoma associated retinal detachment (C). Note marked decrease in height and resolution of the associated retinal detachment (D).
237
238
Fu et al
Table 2 Ultrasonographic features of lesions that simulate choroidal melanoma Lesion
Shape
Reflectivity
Attenuation
Vascularity
Specific Features
Melanoma
Collar button/dome/lobulated
Low-medium
High
High
Choroidal nevus
Flat/Dome
Low-medium
High
No
Choroidal hemangioma
Dome
High
No
No
Metastatic carcinoma ARMD/AREMD
Placoid/irregular/multiple Dome/irregular
Medium-high High
Low No
No No
Leiomyoma
Dome
Low-medium
No
No
Posterior scleritis
Dome
Medium-high
No
No
Regular internal structure Acoustic hollowness Choroidal excavation Height less than 2 mm Regular internal structure Multiple lesions Irregular internal structure Regular internal structure T sign
Abbreviation: ARMD/AREMD, age-related macular and extramacular degeneration.
Intraocular Tumors a uveal melanoma is determined with the transverse and longitudinal approaches of the B-scan. The transverse approach measures the circumferential diameter, while the longitudinal approach evaluates the radial diameter. Intraoperative confirmation of plaque placement Ultrasonagraphy is used commonly to assess proper placement of radioactive material in radiation therapy and evaluate the effectiveness of various treatments. In brachytherapy, localization of a plaque can be performed in the operating room under sterile conditions or postoperatively. It is particularly helpful in posterior tumors, where transillumination cannot indicate the tumor margins adequately. The iodine-125 plaque produces an echolucent pattern with marked shadowing of the orbital tissues (Fig. 12). Response to radiation therapy After radiation treatment, uveal melanoma becomes more irregular and reflective as necrosis
occurs. The tumor loses its internal vascularity and decreases in size, indicating effective treatment (Fig. 13). Some lesions initially enlarge as a result of edema, but most eventually reduce in size. Continued enlargement may signify true tumor growth. Additionally, long-term follow-up is recommended even in lesions with significant initial regression, as tumor growth has been reported in these cases.26,27
Differential Diagnosis of Choroidal Melanoma Several pigmented and nonpigmented lesions can resemble choroidal melanoma. Ultrasonography can be valuable to diagnose and differentiate the more common simulating lesions (Table 2). Circumscribed choroidal hemangioma Uveal hemangioma most frequently affects the choroid and presents as a circumscribed or diffuse orange-red, mildly elevated lesion. Circumscribed tumors are sporadic, usually located in the posterior pole, and dome-shaped with a thickness less
Fig. 14. Circumscribed choroidal hemangioma. Fundus photograph (A). Transverse B-scan demonstrating irregularly shaped choroidal lesion (B). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is highly reflective (C, arrows).
239
240
Fu et al
Fig. 15. Choroidal metastasis. Fundus photograph (A). Transverse B-scan demonstrating dome-shaped choroidal lesion (B). Diagnostic A-scan directed perpendicular to the lesion shows the lesion is slightly irregularly structured and is mainly medium-high reflective (C).
Fig. 16. Leiomyoma. High-frequency ultrasound scan demonstrating ciliary body leiomyoma resembling a melanoma. (From Rundle P, Mudhar HS, Parsons MA, et al. Uveal myogenic, fibrous, and histiocytic tumors. In: Singh AD, Damato BE, Pe’er J, et al, editors. Clinical Ophthalmic Oncology. Philadelphia: Saunders-Elsevier; 2007. p. 312; with permission.)
Fig. 17. Disciform lesion. Longitudinal B-scan demonstrating an irregularly shaped and structured lesion in the macula.
Intraocular Tumors
Fig. 18. Astrocystic hamartoma. Fundus photograph (A). Longitudinal B-scan demonstrating an oval mass with sharp borders and orbital shadowing (B). Diagnostic A-scan directed perpendicular to the lesion shows that the lesion is structured slightly irregularly and is highly reflective (C, arrows).
than 6 mm.28 Diffuse choroidal hemangiomas are a part of neuro-oculo-cutaneous hemangiomatosis (Sturge-Weber syndrome). These tumors often are less elevated than the circumscribed, domeshaped lesions and can be mistaken for nonspecific retinochoroidal thickening. As a result, the retinochoroid layer thickness must be compared carefully between the two eyes in cases with Sturge-Weber syndrome. On A-scan, choroidal hemangiomas exhibit high internal reflectivity with negligible attenuation. They are hyperechoic on B-scan with regular internal structure and little internal blood flow (Fig. 14). Serous retinal detachment at the tumor margins and calcification on the tumor surface may be present.28
degree of internal irregularity that results from the varied histologic architecture (Fig. 15). Internal vascularity is minimal or absent. On B-scan, these lesions have irregular surfaces and often central excavations. The serous retinal detachment is often much more extensive with metastatic carcinomas than with a comparable-sized choroidal melanoma. Vitreous and subretinal hemorrhages rarely are associated with metastatic carcinoma. Some choroidal metastases present with atypical features such as low internal reflectivity and internal vascularity. The most common metastasis to produce these atypical findings is small cell carcinoma of the lung. Additionally, bullous choroidal detachments have been reported.29
Choroidal metastasis Choroidal metastasis preferentially presents in the posterior pole as focal or multifocal lesions. They may be flat or dome-shaped, pigmented or nonpigmented, and unilateral or bilateral. They frequently are associated with serous retinal detachments. The internal reflectivity of metastatic carcinoma is typically medium to high with some
Leiomyoma Leiomyoma is a nonpigmented benign tumor that almost exclusively occurs in young women. Clinically, they can be differentiated from amelanotic choroidal melanoma by transillumination. Leiomyoma readily transilluminates, while choroidal melanoma does not. On B-scan, these lesions are smooth and dome-shaped. A scan shows
241
242
Fu et al
Box 2 Conditions associated with intraocular calcification Retinal and RPE lesions Retinoblastoma Astrocytic hamartoma Chronic retinal detachment RPE metaplasia Cysticercosis Choroidal lesions Choroidal osteoma Sclerochoroidal calcification Choroidal granuloma Others Optic nerve head drusen Scleral calcification (Cogan’s plaque) Phthisis bulbi
low-to-medium internal reflectivity with regular internal structure (Fig. 16).
Age-related macular and extramacular degeneration Exudative age-related macular and extramacular degeneration (ARMD/AREMD) with subretinal or sub-retinal pigment epithelium exudate or hemorrhage can resemble choroidal melanoma closely. Ultrasonographically, exudative ARMD/AREMD appears as a mass lesion with moderately high internal reflectivity. When the subretinal blood becomes organized, however, these lesions can display low internal reflectivity and choroidal
excavation, similar to that seen with a choroidal melanoma. Scarring, fibrosis, and calcification can occur in chronic stages of exudative ARMD/AREMD, leading to the formation of disciform lesions. Nonhemorrhagic disciform lesions appear as two or three highly reflective spikes on A-scan. On B-scan, they are mildly to moderately elevated, dome-shaped, and heterogeneous (see the article by Sharma and colleagues, elsewhere in this issue). Hemorrhagic disciform lesions can be localized or diffuse. They usually exhibit a bumpy, lobulated surface with indistinct margins. On ultrasonography, they display irregular internal structure with areas of high and low internal reflectivity as a result of fibrovascular proliferation, exudation, and clotted or unclotted hemorrhage (Fig. 17). Calcification and vitreous hemorrhage can be associated with these lesions. Unlike choroidal melanoma, internal vascularity is not present in these lesions. Serial examination of hemorrhagic disciform lesions can help distinguish them from choroidal melanomas. Hemorrhagic disciform lesions tend to decrease in size, whereas choroidal melanomas remain stable or increase in size. Very rarely, spontaneous regression of choroidal melanoma can occur.30 Posterior scleritis Nodular posterior scleritis appears as an elevated mass that can resemble an amelanotic choroidal melanoma closely. Ultrasonographic features of these lesions are described in the article by Ventura and colleagues, elsewhere in this issue.
INTRAOCULAR CALCIFICATION Intraocular calcification can result from several tumors and degenerative processes (Box 2).
Fig. 19. Choroidal osteoma. Fundus photograph (A). Vertical axial B-scan demonstrating a minimally elevated, highly reflective lesion causing orbital shadowing (B).
Intraocular Tumors
Fig. 20. Sclerochoroidal calcification. Fundus photograph (A). Transverse B-scan demonstrating an irregularly shaped, highly reflective fundus lesion with orbital shadowing (B).
Astrocytic Hamartoma
Others
Astrocytic hamartoma of the retina and optic disc is a benign tumor that typically occurs in patients who have tuberous sclerosis and neurofibromatosis. Small, noncalcified tumors can be extremely subtle and appear as ill-defined translucent thickening of the nerve fiber layer. Larger lesions become more opaque and appear as a sessile white lesion at the level of the nerve fiber layer. Some lesions contain characteristic dense yellow, refractile calcification that has been likened to mulberry or tapioca. Ultrasonography is of little diagnostic value in small, flat, noncalcified lesions. Larger calcified lesions, however, appear as welldemarcated oval masses with a high reflectivity, sharp anterior borders, and orbital shadowing on B-scan. A scan shows high internal reflectivity and attenuation of orbital echoes posterior to the tumor (Fig. 18).
Cogan’s plaques are focal areas of scleral calcification located anterior to the insertion of the horizontal rectii muscles. Chronic ocular inflammation or trauma can induce osseous metaplasia of the RPE with or without phthisis bulbi, which can be detected as intraocular calcification by ultrasonography.
Choroidal Osteoma Choroidal osteomas are composed of cancellous bone and present as yellow-white, minimally elevated, well-defined lesions in the juxtapapillary or peripapillary region. These lesions produce extremely high internal reflectivity on A-scan. They are very echo-dense on B-scan with significant orbital shadowing (Fig. 19).
Sclerochoroidal Calcification Sclerochoroidal calcification simulates choroidal osteoma ultrasonographically with high reflectivity and marked orbital shadowing. Distinction between these two entities is based on clinical features (Fig. 20).
REFERENCES 1. Shields CL, Shields JA, Shah P. Retinoblastoma in older children. Ophthalmology 1991;98:395–9. 2. All-Ericsson C, Economou MA, Landau I, et al. Uveitis masquerade syndromes: diffuse retinoblastoma in an older child. Acta Ophthalmol Scand 2007;85:569–70. 3. Ridley ME, Shields JA, Brown GC, et al. Coats’ disease. Evaluation of management. Ophthalmology 1982;89:1381–7. 4. Jaffe MS, Shields JA, Canny CL, et al. Retinoblastoma simulating Coats’ disease: a clinicopathologic report. Ann Ophthalmol 1977;9:863–8. 5. Shields JA, Eagle RC Jr, Shields CL, et al. Congenital neoplasms of the nonpigmented ciliary epithelium (medulloepithelioma). Ophthalmology 1996; 103:1998–2006. 6. Broughton WL, Zimmerman LE. A clinicopathologic study of 56 cases of intraocular medulloepitheliomas. Am J Ophthalmol 1978;85:407–18. 7. Morris AT, Garner A. Medulloepithelioma involving the iris. Br J Ophthalmol 1975;59:276–8. 8. Orellana J, Moura RA, Font RL, et al. Medulloepithelioma diagnosed by ultrasound and vitreous aspirate. Electron microscopic observations. Ophthalmology 1983;90:1531–9. 9. Green WR, Iliff WJ, Trotter RR. Malignant teratoid medulloepithelioma of the optic nerve. Arch Ophthalmol 1974;91:451–4.
243
244
Fu et al 10. Biswas J, Bhushan B, Jayakumar N, et al. Teratoid malignant medulloepithelioma of the optic nerve: report of a case and review of the literature. Orbit 1999;18:191–6. 11. Factors predictive of growth and treatment of small choroidal melanoma: COMS Report No. 5. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol 1997;115:1537–44. 12. Brownstein S, Dorey MW, Mathew B, et al. Melanocytoma of the choroid: atypical presentation and review of the literature. Can J Ophthalmol 2002;37(4):247–52. 13. Demirci H, Mashayekhi A, Shields CL, et al. Iris melanocytoma: clinical features and natural course in 47 cases. Am J Ophthalmol 2005;139:468–75. 14. LoRusso FJ, Boniuk M, Font RL. Melanocytoma (magnocellular nevus) of the ciliary body: report of 10 cases and review of the literature. Ophthalmology 2000;107:795–800. 15. Shields JA, Demirci H, Mashayekhi A, et al. Melanocytoma of optic disc in 115 cases: the 2004 Samuel Johnson Memorial Lecture, part 1. Ophthalmology 2004;111:1739–46. 16. Reidy JJ, Apple DJ, Steinmetz RL, et al. Melanocytoma: nomenclature, pathogenesis, natural history, and treatment. Surv Ophthalmol 1985;29: 319–27. 17. Mansour AM, Zimmerman L, La Piana FG, et al. Clinicopathological findings in a growing optic nerve melanocytoma. Br J Ophthalmol 1989;73:410–5. 18. Roth AM. Malignant change in melanocytomas of the uveal tract. Surv Ophthalmol 1978;22:404–12. 19. Apple DJ, Craythorn JM, Reidy JJ, et al. Malignant transformation of an optic nerve melanocytoma. Can J Ophthalmol 1984;19:320–5. 20. Meyer D, Ge J, Blinder KJ, et al. Malignant transformation of an optic disk melanocytoma. Am J Ophthalmol 1999;127:710–4.
21. Goldberg MF, Hodes BL. Ultrasonographic diagnosis of choroidal malignant melanoma. Surv Ophthalmol 1977;22:29–40. 22. Fuller DG, Snyder WB, Hutton WL, et al. Ultrasonographic features of choroidal malignant melanomas. Arch Ophthalmol 1979;97:1465–72. 23. Cham MC, Pavlin CJ. Ultrasound detection of posterior scleral bowing in young patients with choroidal melanoma. Can J Ophthalmol 2000;35: 263–6. 24. Braun UC, Rummelt VC, Naumann GO. Diffuse maligne Melanome der Uvea. Eine klinisch-histopathologische Studie uber 39 Patienten. Klin Monatsbl Augenheilkd 1998;213:331–40. 25. Biswas J, Raghavendra R, Ratra V, et al. Diffuse malignant melanoma of the choroid-simulating metastatic tumour in the choroid. Indian J Ophthalmol 2000;48:137–40. 26. Gragoudas ES, Lane AM, Munzenrider J, et al. Long-term risk of local failure after proton therapy for choroidal/ciliary body melanoma. Trans Am Ophthalmol Soc 2002;100:43–8. 27. Novak-Andrejcic K, Jancar B, Hawlina M. Echographic follow-up of malignant melanoma of the choroid after brachytherapy with 106Ru. Klin Monatsbl Augenheilkd 2003;220:853–60. 28. Witschel H, Font RL. Hemangioma of the choroid. A clinicopathologic study of 71 cases and a review of the literature. Surv Ophthalmol 1976;20:415–31. 29. Kreiger AE, Meyer D, Smith TR, et al. Metastatic carcinoma to the choroid with choroidal detachment. A case presenting as uveal effusion. Arch Ophthalmol 1969;82:209–13. 30. Shields CL, Shields JA, Santos MC, et al. Incomplete spontaneous regression of choroidal melanoma associated with inflammation. Arch Ophthalmol 1999; 117:1245–7.